Maternal Plasma Concentrations of angiogenic/antiangiogenic Factors in the Third Trimester of Pregnancy to Identify the Patient at Risk for Stillbirth at or Near Term and Severe Late Preeclampsia

Am J Obstet Gynecol. 2013 Apr;208(4):287.e1-287.e15. doi: 10.1016/j.ajog.2013.01.016. Epub 2013 Jan 17.


Objective: To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30-34 weeks of gestation can identify patients at risk for stillbirth, late preeclampsia, and delivery of small-for-gestational-age (SGA) neonates.

Study design: A prospective cohort study included 1269 singleton pregnant women from whom blood samples were obtained at 30-34 weeks of gestation and who delivered at >34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by enzyme-linked immunosorbent assay.

Results: The prevalence of late (>34 weeks of gestation) preeclampsia, severe late preeclampsia, stillbirth, and SGA was 3.2% (n = 40), 1.8% (n = 23), 0.4% (n = 5), and 8.5% (n = 108), respectively. A plasma concentration of PlGF/sEng <0.3 MoM was associated with severe late preeclampsia (adjusted odds ratio, 16); the addition of PlGF/sEng to clinical risk factors increased the area under the receiver-operating characteristic curve from 0.76 to 0.88 (P = .03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20-25 weeks of gestation for the prediction of severe late preeclampsia (comparison of areas under the receiver-operating characteristic curve; each P ≤ .02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false-positive rate of 15% for the identification of severe late preeclampsia. A plasma concentration of PlGF/sVEGFR-1 <0.12 MoM at 30-34 weeks of gestation had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80%; specificity 93%) were observed in a separate case-control study.

Conclusion: Risk assessment for stillbirth and severe late preeclampsia in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and antiangiogenic factors at 30-34 weeks of gestation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Angiogenesis Inducing Agents / blood
  • Angiogenesis Inhibitors / blood
  • Angiogenesis Modulating Agents / blood*
  • Antigens, CD / blood*
  • Biomarkers / blood
  • Endoglin
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age / blood
  • Placenta Growth Factor
  • Pre-Eclampsia / blood*
  • Pregnancy
  • Pregnancy Proteins / blood*
  • Pregnancy Trimester, Third
  • Prospective Studies
  • Receptors, Cell Surface / blood*
  • Risk Assessment
  • Risk Factors
  • Stillbirth*
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Young Adult


  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Angiogenesis Modulating Agents
  • Antigens, CD
  • Biomarkers
  • ENG protein, human
  • Endoglin
  • PGF protein, human
  • Pregnancy Proteins
  • Receptors, Cell Surface
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1